EP0271833A2 - Process for the preparation of aminopyrimidines - Google Patents

Process for the preparation of aminopyrimidines Download PDF

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Publication number
EP0271833A2
EP0271833A2 EP87118369A EP87118369A EP0271833A2 EP 0271833 A2 EP0271833 A2 EP 0271833A2 EP 87118369 A EP87118369 A EP 87118369A EP 87118369 A EP87118369 A EP 87118369A EP 0271833 A2 EP0271833 A2 EP 0271833A2
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Prior art keywords
alkyl
formula
phenyl
halo
alkoxy
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German (de)
French (fr)
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EP0271833B1 (en
EP0271833A3 (en
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Stephen Dr. Lachhein
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Bayer CropScience AG
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Hoechst AG
Hoechst Schering Agrevo GmbH
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/56—One oxygen atom and one sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/58—Two sulfur atoms

Definitions

  • the invention relates to a process for the preparation of pyrimidines of the formula I.
  • X and Y independently of one another oxygen or sulfur and R1 and R2 independently of one another denote (C1-C4) alkyl, (C1-C4) alkoxy- (C1-C2) alkyl or halo (C1-C4) alkyl, characterized in that a propanediimidate of the formula II wherein R1 and R2 are as defined in Formula I, or one of its salts with a cyanate ester of the formula III R3-OC ⁇ N III, wherein R3 (C1-C4) alkyl, phenyl, phenyl which is substituted by 1, 2 or 3 radicals from the radicals halogen, (C1-C4) alkoxy and (C1-C4) alkyl, ⁇ - or ⁇ -naphthyl or halo ( C1-C4) alkyl means reacted in an inert organic solvent.
  • pyrimidines of the formula I can be prepared by reacting propanediimidates with aqueous cyanamide solution or cyanogen chloride in a two- or three-stage process (EP-A-0 024 200), the formation and subsequent isolation of an N-cyanoimidate as an intermediate as characteristic process features are to be viewed.
  • the yields available for the end product are unsatisfactory.
  • Further disadvantages of the process mentioned are: the formation of not inconsiderable amounts of by-products, the need to carry out the reaction in a narrow pH range and the additional use of a base.
  • a further disadvantage is that the inorganic salts formed during the reaction, especially when using aqueous cyanamide solution, get into the waste water in dissolved form, from which they have to be removed by additional measures.
  • the process according to the invention surprisingly proceeds in a process-technically simple manner
  • One-step process without isolable intermediates which allows a reaction to be carried out without pH control.
  • By-products are only formed to a minor extent.
  • the imide nitrogen attacks the cyanate ester without a cyanimidate passing through or being formed as an intermediate stage.
  • the high selectivity in the formation of compounds of the formula I and the associated high yields were not to be expected.
  • the process according to the invention is expediently carried out in such a way that the propanediimidate is isolated as the mono- or disalt or as the bisimidate, in solution or as a suspension with the cyanate ester of the formula III at reaction temperatures of 0-180 ° C., preferably 20-140 ° C. .
  • Preferred salts of propanediimidate are those of hydrofluoric, hydrochloric or hydrobromic acid or sulfuric or phosphoric acid.
  • Haloalkyl radicals for R1, R2, R3 are, for example, CH2Cl, CHCl2, CCl3, CH2CH2Cl or CH2CF3.
  • X and Y are preferably oxygen.
  • R1 and R2 are preferably (C1-C4) alkyl, especially methyl.
  • R3 is preferably phenyl, which can have up to 3 substituents, in particular 1 or 2 substituents, from the radicals chlorine, methyl and methoxy, or ⁇ -naphthy
  • Suitable inert organic solvents are those which are inert under the respective reaction conditions.
  • alcohols such as methanol, ethanol and propanol
  • ketones such as acetone and methyl isobutyl ketone
  • ethers such as diethyl ether, dioxane and tetrahydrofuran
  • esters such as methyl acetate, ethyl acetate and butyl acetate
  • hydrocarbons such as toluene, xylene, hexane and cyclohexane
  • nitroles such as acetonitrile
  • halogenated hydrocarbons such as chloroform and methylene chloride or mixtures of the solvents listed.
  • the compounds of formula II can be prepared by known methods (SM McElvain and ID Schroeder, JACS 71 , 40 (1949); B. Harstun, DE-OS 2426913).
  • the mono salt and the bisimidate of these compounds can be prepared from the corresponding disalt by reaction with bases such as alkali and alkaline earth metal hydroxides, carbonates, bicarbonates or alcoholates in an inert solvent.
  • bases such as alkali and alkaline earth metal hydroxides, carbonates, bicarbonates or alcoholates in an inert solvent.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Pyrimidine der Formel I, <IMAGE> worin X und Y Sauerstoff oder Schwefel und R¹ und R² C1-C4-Alkyl, (C1-C4-Alkoxy)-C1-C2-alkyl oder Halo-C1-C4-alkyl bedeuten, werden durch Umsetzung von Propandiimidaten der Formel II R¹ - X - ?? - CH2 - ?? - Y - R² II oder deren Salze mit Cyansäureestern der Formel R³-O-CN, worin R³ C1-C4-Alkyl, Phenyl, Phenyl, das durch 1, 2 oder 3 Reste aus den Resten Halogen, C1-C4-Alkoxy und C1-C4-Alkyl substituiert ist, α- oder β-Naphthyl oder Halo-C1-C4-alkyl bedeutet, in einem unter den Reaktionsbedingungen inerten organischen Lösungsmittel erhalten. Das Einstufenverfahren gestattet eine effektive Herstellung der Verbindungen der Formel I, die als Zwischenprodukte zur Herstellung herbizider Sulfonylharnstoffe verwendet werden können.Pyrimidines of the formula I, <IMAGE> in which X and Y are oxygen or sulfur and R 1 and R 2 are C1-C4-alkyl, (C1-C4-alkoxy) -C1-C2-alkyl or halo-C1-C4-alkyl, are by Implementation of propanediimidates of the formula II R¹ - X - ?? - CH2 - ?? - Y - R² II or their salts with cyanate esters of the formula R³-O-CN, in which R³ is C1-C4-alkyl, phenyl, phenyl, which is formed by 1, 2 or 3 radicals from the radicals halogen, C1-C4-alkoxy and C1 -C4-alkyl is substituted, α- or β-naphthyl or halo-C1-C4-alkyl means, obtained in an organic solvent which is inert under the reaction conditions. The one-step process permits effective preparation of the compounds of formula I which can be used as intermediates for the preparation of herbicidal sulfonylureas.

Description

Gegenstand der Erfindung ist ein Verfahren zur Herstellung von Pyrimidinen der Formel I

Figure imgb0001
worin
X und Y unabhängig voneinander Sauerstoff oder Schwefel und
R¹ und R² unabhängig voneinander (C₁-C₄)Alkyl, (C₁-C₄)Alkoxy-­(C₁-C₂)alkyl oder Halo(C₁-C₄)alkyl bedeuten,
dadurch gekennzeichnet, daß man ein Propandiimidat der Formel II
Figure imgb0002
 worin R¹ und R² wie bei Formel I definiert sind, oder eines seiner Salze
mit einem Cyansäureester der Formel III
R³-O-C≡N      III,
worin
R³ (C₁-C₄)Alkyl, Phenyl, Phenyl, das durch 1, 2 oder 3 Reste aus den Resten Halogen, (C₁-C₄)Alkoxy und (C₁-C₄)Alkyl substituiert ist, α- oder β-Naphthyl oder Halo(C₁-C₄)alkyl bedeutet,
in einem inerten organischen Lösungsmittel umsetzt.The invention relates to a process for the preparation of pyrimidines of the formula I.
Figure imgb0001
 wherein
X and Y independently of one another oxygen or sulfur and
R¹ and R² independently of one another denote (C₁-C₄) alkyl, (C₁-C₄) alkoxy- (C₁-C₂) alkyl or halo (C₁-C₄) alkyl,
characterized in that a propanediimidate of the formula II
Figure imgb0002
 wherein R1 and R2 are as defined in Formula I, or one of its salts
with a cyanate ester of the formula III
R³-OC≡N III,
wherein
R³ (C₁-C₄) alkyl, phenyl, phenyl which is substituted by 1, 2 or 3 radicals from the radicals halogen, (C₁-C₄) alkoxy and (C₁-C₄) alkyl, α- or β-naphthyl or halo ( C₁-C₄) alkyl means
reacted in an inert organic solvent.

Verbindungen der Formel I sind wertvolle Zwischenprodukte bei der Herstellung von Sulfonylharnstoffen mit herbizider Wirkung; siehe beispielsweise US-A-4,169,179 oder EP-A-071 958 (US-A-4,492,598).Compounds of the formula I are valuable intermediates in the preparation of sulfonylureas with a herbicidal action; see for example US-A-4,169,179 or EP-A-071 958 (US-A-4,492,598).

Bekannt ist die Umsetzung von Nucleophilen und Dinucleophilen mit Cyansäureestern (E. Grigat, Angew. Chem. 84, 1008 (1972); Angew. Chem. Int. Ed. Vol 11, 949 (1972)).The reaction of nucleophiles and dinucleophiles with cyanate esters is known (E. Grigat, Angew. Chem. 84 , 1008 (1972); Angew. Chem. Int. Ed. Vol 11, 949 (1972)).

Ferner ist bekannt, daß Pyrimidine der Formel I durch Umsetzung von Propandiimidaten mit wäßriger Cyanamidlösung oder Chlorcyan in einem Zwei- oder Dreistufenprozeß hergestellt werden können (EP-A-0 024 200), wobei die Bildung und anschließende Isolierung eines N-Cyanoimidates als Zwischenprodukt als charakteristische Verfahrensmerkmale anzusehen sind. Die hierbei erhältlichen Ausbeuten für das Endprodukt sind jedoch unbefriedigend. Weitere Nachteile des genannten Verfahrens sind: die Bildung nicht unerheblicher Mengen an Nebenprodukten, die Notwendigkeit der Reaktionsführung in einem engen pH-Bereich und die zusätzliche Verwendung einer Base. Außerdem ist von Nachteil, daß die während der Umsetzung gebildeten anorganischen Salze, speziell beim Einsatz von wäßriger Cyanamidlösung, in gelöster Form ins Abwasser gelangen, aus welchem sie durch zusätzliche Maßnahmen entfernt werden müssen.It is also known that pyrimidines of the formula I can be prepared by reacting propanediimidates with aqueous cyanamide solution or cyanogen chloride in a two- or three-stage process (EP-A-0 024 200), the formation and subsequent isolation of an N-cyanoimidate as an intermediate as characteristic process features are to be viewed. The yields available for the end product are unsatisfactory. Further disadvantages of the process mentioned are: the formation of not inconsiderable amounts of by-products, the need to carry out the reaction in a narrow pH range and the additional use of a base. A further disadvantage is that the inorganic salts formed during the reaction, especially when using aqueous cyanamide solution, get into the waste water in dissolved form, from which they have to be removed by additional measures.

Überraschenderweise verläuft das erfindungsgemäße Verfahren demgegenüber in einem verfahrenstechnisch einfachen Einstufenprozeß ohne isolierbare Zwischenprodukte, der eine Reaktionsführung ohne pH-Kontrolle gestattet. Nebenprodukte werden nur in untergeordnetem Maß gebildet.In contrast, the process according to the invention surprisingly proceeds in a process-technically simple manner One-step process without isolable intermediates, which allows a reaction to be carried out without pH control. By-products are only formed to a minor extent.

Beim erfindungsgemäßen Verfahren greift der Imidstickstoff am Cyansäureester an, ohne daß dabei ein Cyanimidat als Zwischenstufe durchlaufen oder gebildet wird. Die hohe Selektivität bei der Bildung von Verbindungen der Formel I und die damit verbundenen hohen Ausbeuten waren nicht zu erwarten.In the process according to the invention, the imide nitrogen attacks the cyanate ester without a cyanimidate passing through or being formed as an intermediate stage. The high selectivity in the formation of compounds of the formula I and the associated high yields were not to be expected.

Im Verlauf der Reaktion werden keine Salze gebildet, die zu einer Abwasserbelastung führen könnten. Neben den bereits beschriebenen verfahrenstechnischen und wirtschaftlichen Vorteilen, ist dieser Aspekt aus ökologischer Sicht als fortschrittlich anzusehen. Nach Beendigung der Reaktion, Extraktion des gebildeten Alkohols (R³OH) und Abdestillieren des Lösungsmittel, welches nahezu quantitativ zurückgewonnen wird, verbleibt des Endprodukt in hoher Reinheit.No salts are formed in the course of the reaction which could lead to wastewater pollution. In addition to the procedural and economic advantages already described, this aspect is to be regarded as progressive from an ecological point of view. After completion of the reaction, extraction of the alcohol formed (R³OH) and distilling off the solvent, which is recovered almost quantitatively, the end product remains in high purity.

Das erfindungsgemäße Verfahren wird zweckmäßigerweise so durchgeführt, daß man das Propandiimidat alsk Mono- oder Disalz oder als Bisimidat isoliert, in Lösung oder als Suspension mit dem Cyansäureester der Formel III bei Reaktionstemperaturen von 0-180 °C, vorzugsweise 20-140 °C, umsetzt. Als Salze des Propandiimidates werden bevorzugt solche der Fluor-, Chlor- oder Bromwasserstoffsäure oder der Schwefel- oder Phosphorsäure eingesetzt. Haloalkylreste für R¹, R², R³ sind beispielsweise CH₂Cl, CHCl₂, CCl₃, CH₂CH₂Cl oder CH₂CF₃. Vorzugsweise bedeuten X und Y Sauerstoff. R¹ und R² bedeuten vorzugsweise (C₁-C₄)Alkyl, insbesondere Methyl. R³ bedeutet vorzugsweise Phenyl, das bis zu 3 Substituenten, insbesondere 1 oder 2 Substituenten, aus den Resten Chlor, Methyl und Methoxy aufweisen kann, oder β-Naphthyl.The process according to the invention is expediently carried out in such a way that the propanediimidate is isolated as the mono- or disalt or as the bisimidate, in solution or as a suspension with the cyanate ester of the formula III at reaction temperatures of 0-180 ° C., preferably 20-140 ° C. . Preferred salts of propanediimidate are those of hydrofluoric, hydrochloric or hydrobromic acid or sulfuric or phosphoric acid. Haloalkyl radicals for R¹, R², R³ are, for example, CH₂Cl, CHCl₂, CCl₃, CH₂CH₂Cl or CH₂CF₃. X and Y are preferably oxygen. R¹ and R² are preferably (C₁-C₄) alkyl, especially methyl. R³ is preferably phenyl, which can have up to 3 substituents, in particular 1 or 2 substituents, from the radicals chlorine, methyl and methoxy, or β-naphthyl.

Als inerte organische Lösungsmittel sind solche geeignet, die unter den jeweiligen Reaktionsbedingungen inert sind. Beispielsweise können als inerte organische Lösungsmittel Alkohole wie Methanol, Ethanol, und Propanol, Ketone wie Aceton und Methylisobutylketon, Ether wie Diethylether, Dioxan und Tetrahydrofuran, Ester wie Methylacetat, Ethylacetat und Butylacetat, Kohlenwasserstoffe wie Toluol, Xylol, Hexan und Cyclohexan, Nitrole wie Acetonitril und halogenierte Kohlenwasserstoffe wie Chloroform und Methylenchlorid oder Mischungen der aufgeführten Lösungsmittel verwendet werden.Suitable inert organic solvents are those which are inert under the respective reaction conditions. For example, alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl isobutyl ketone, ethers such as diethyl ether, dioxane and tetrahydrofuran, esters such as methyl acetate, ethyl acetate and butyl acetate, hydrocarbons such as toluene, xylene, hexane and cyclohexane, nitroles such as acetonitrile can be used as the inert organic solvents and halogenated hydrocarbons such as chloroform and methylene chloride or mixtures of the solvents listed.

Um störende Einflüsse von Sauerstoff auf die Reaktion zu vermeiden, ist es zweckmäßig, unter Inertgasatmosphäre, beispielsweise unter Stickstoff, zu arbeiten.In order to avoid disturbing influences of oxygen on the reaction, it is expedient to work under an inert gas atmosphere, for example under nitrogen.

Die Verbindungen der Formel II können nach bekannten Methoden hergestellt werden (S.M. McElvain and I.D. Schroeder, JACS 71, 40 (1949); B. Harstun, DE-OS 2426913).The compounds of formula II can be prepared by known methods (SM McElvain and ID Schroeder, JACS 71 , 40 (1949); B. Harstun, DE-OS 2426913).

Das Monosalz und das Bisimidat dieser Verbindungen können aus dem entsprechenden Disalz durch Umsetzung mit Basen wie Alkali- und Erdalkalihydroxiden, -carbonaten, -hydrogencarbonaten oder -alkoholaten in einem inerten Lösungsmittel hergestellt werden.The mono salt and the bisimidate of these compounds can be prepared from the corresponding disalt by reaction with bases such as alkali and alkaline earth metal hydroxides, carbonates, bicarbonates or alcoholates in an inert solvent.

Nachfolgende Beispiele sollen das erfindungsgemäße Verfahren näher erläutern:The following examples are intended to explain the process according to the invention in more detail:

Beispiel 1example 1

Zu 800 ml Diethylether werden bei Raumtemperatur unter Stickstoffüberlagerung 52 g Dimethylpropandiimidat und 49 g Phenylcyanat gegeben. Nach 5 Stunden Erwärmen auf 36 °C wird das Phenol mit 10 %iger Natronlauge ausgewaschen und das Lösungsmittel abdestilliert.52 g of dimethylpropane diimidate and 49 g of phenyl cyanate are added to 800 ml of diethyl ether at room temperature with a blanket of nitrogen. After heating for 5 hours at 36 ° C., the phenol is washed out with 10% sodium hydroxide solution and the solvent is distilled off.

Es verbleiben 55 g Produkt, was einer Ausbeute von 89 % der Theorie entspricht.
Der Schmelzpunkt beträgt 93-94 °C.55 g of product remain, which corresponds to a yield of 89% of theory.
The melting point is 93-94 ° C.

Beispiel 2Example 2

Zu 800 ml Methylisobutylketon werden unter Stickstoffüberlagerung bei 50 °C 49 g Phenylcyanat und 52 g Dimethylpropandiimidat gegeben und für 5 Stunden reagieren gelassen. Das entstehende Phenol wird mit Natronlauge extrahiert und das Lösungsmittel abdestilliert. Es verbleiben 56,4 g Produkt, was einer Ausbeute von 91 % der Theorie entspricht. Der Schmelzpunkt beträgt 92-94 °C.49 g of phenyl cyanate and 52 g of dimethylpropane diimidate are added to 800 ml of methyl isobutyl ketone under a blanket of nitrogen at 50 ° C. and left to react for 5 hours. The resulting phenol is extracted with sodium hydroxide solution and the solvent is distilled off. 56.4 g of product remain, which corresponds to a yield of 91% of theory. The melting point is 92-94 ° C.

Beispiel 3Example 3

In einer Lösung von 500 ml Aceton werden unter Stickstoffüberlagerung bei 40 °C 52 g Dimethylpropandiimidat und 75,2 g 2,4-Dichlorphenylcyanat gegeben und 5 Stunden bei 40 °C reagieren gelassen. Nach Extrahieren von 2,4-Dichlorphenol wird das Lösungsmittel abdestilliert.
Es verbleiben 54,5 g Produkt, was einer Ausbeute von 88 % der Theorie entspricht.
Der Schmelzpunkt ist 92-94 °C.52 g of dimethylpropane diimidate and 75.2 g of 2,4-dichlorophenyl cyanate are added to a solution of 500 ml of acetone under a blanket of nitrogen at 40 ° C. and the mixture is left to react at 40 ° C. for 5 hours. After extracting 2,4-dichlorophenol, the solvent is distilled off.
54.5 g of product remain, which corresponds to a yield of 88% of theory.
The melting point is 92-94 ° C.

Beispiel 4Example 4

Zu 500 ml Essigsäuremethylester werden 59 g 2,4-Dimethylphenylcyanat und 67 g Dimethylpropandiimidatmonohydrochlorid gegeben und 5 Stunden bei 50 °C reagieren gelassen. Nach Extrahieren von 2,4-Dimethylphenol mit Natronlauge wird das Lösungsmittel abdestilliert.
Es verbleiben 53 g Produkt, was einer Ausbeute von 86 % der Theorie entspricht.
Der Schmelzpunkt beträgt 92-93 °C.59 g of 2,4-dimethylphenyl cyanate and 67 g of dimethylpropane diimidate monohydrochloride are added to 500 ml of methyl acetate and the mixture is left to react at 50 ° C. for 5 hours. After extracting 2,4-dimethylphenol with sodium hydroxide solution, the solvent is distilled off.
53 g of product remain, which corresponds to a yield of 86% of theory.
The melting point is 92-93 ° C.

Beispiel 5Example 5

Zu 500 ml Toluol werden bei 70 °C 52 g Dimethylpropandiimidat und 63 g β-Naphthylcyanat gegeben und 5 Stunden bei 70 °C reagieren gelassen. Nach Entfernen des β-Naphthols wird das Lösungsmittel abdestilliert. Es verbleiben 55,8 g Produkt, was einer Ausbeute von 90 % der Theorie entspricht.52 g of dimethylpropane diimidate and 63 g of β-naphthyl cyanate are added to 500 ml of toluene at 70 ° C. and the mixture is left to react at 70 ° C. for 5 hours. After removing the β-naphthol, the solvent is distilled off. 55.8 g of product remain, which corresponds to a yield of 90% of theory.

Beispiel 6Example 6

Zu 800 ml Toluol werden unter Stickstoffüberlagerung bei 110 °C 52 g Dimethylpropandiimidat und 67,0g 2-Methyl-4-­chlorphenylcyanat gegeben und 5 Stunden bei 110 °C reagieren gelassen. Nach Extraktion von 2-Methyl-4-­chlorphenol wird das Lösungsmittel abdestilliert. Es verbleiben 55,2 g Produkt, was einer Ausbeute von 89,2 % der Theorie entspricht.
Der Schmelzpunkt des Produkts ist 92-94 °C.52 g of dimethylpropane diimidate and 67.0 g of 2-methyl-4-chlorophenyl cyanate are added to 800 ml of toluene under a blanket of nitrogen at 110 ° C. and the mixture is left to react at 110 ° C. for 5 hours. After extraction of 2-methyl-4-chlorophenol, the solvent is distilled off. 55.2 g of product remain, which corresponds to a yield of 89.2% of theory.
The melting point of the product is 92-94 ° C.

Beispiel 7Example 7

Zu 800 ml Toluol werden unter Stickstoffüberlagerung bei 90 °C 52 g Dimethylpropandiimidat und 73,4g 4-Chlor-2-­methoxyphenylcyanat gegeben und 6 Stunden bei 90 °C reagieren gelassen. Nach Extraktion von 4-Chlor-2-­methoxyphenol wird das Lösungsmittel abdestilliert. Es verbleiben 53,2 g Produkt (Ausbeute 86 % d. Th.) mit einem Schmelzpunkt von 92-93 °C.52 g of dimethylpropane diimidate and 73.4 g of 4-chloro-2-methoxyphenyl cyanate are added to 800 ml of toluene under a blanket of nitrogen at 90 ° C. and the mixture is left to react at 90 ° C. for 6 hours. After extraction of 4-chloro-2-methoxyphenol, the solvent is distilled off. There remain 53.2 g of product (yield 86% of theory) with a melting point of 92-93 ° C.

Beispiel 8-19Example 8-19

Analog zu den in den Beispielen 1-7 beschriebenen Verfahrensweisen lassen sich beispielsweise folgende Verbindungen der Formel I herstellen:

Figure imgb0003
The following compounds of the formula I can be prepared analogously to the procedures described in Examples 1-7:
Figure imgb0003

Claims (8)

1. Verfahren zur Herstellung von Verbindungen der Formel I
Figure imgb0004
 worin
X und Y unabhängig Sauerstoff oder Schwefel und
R¹ und R² unabhängig voneinander (C₁-C₄)Alkyl, (C₁-C₄)Alkoxy-(C₁-C₂)alkyl oder Halo(C₁-C₄)alkyl bedeuten,
dadurch gekennzeichnet, daß man ein Propandiimidat der Formel II
Figure imgb0005
 worin R¹ und R² wie bei Formel I definiert sind, oder eines seiner Salze
mit einem Cyansäureester der Formel III
R³-O-C≡N      III,
worin
R³ (C₁-C₄)Alkyl, Phenyl, Phenyl, das durch 1, 2, oder 3 Reste aus den Resten Halogen, (C₁-C₄)Alkoxy oder (C₁-C₄)Alkyl substituiert ist, α- oder β-Naphthyl oder Halo(C₁-C₄)alkyl bedeutet,
in einem inerten organischen Lösungsmittel umsetzt.1. Process for the preparation of compounds of formula I.
Figure imgb0004
 wherein
X and Y are independently oxygen or sulfur and
R¹ and R² independently of one another denote (C₁-C₄) alkyl, (C₁-C₄) alkoxy- (C₁-C₂) alkyl or halo (C₁-C₄) alkyl,
characterized in that a propanediimidate of the formula II
Figure imgb0005
 wherein R1 and R2 are as defined in Formula I, or one of its salts
with a cyanate ester of the formula III
R³-OC≡N III,
wherein
R³ (C₁-C₄) alkyl, phenyl, phenyl, which is substituted by 1, 2 or 3 radicals from the radicals halogen, (C₁-C₄) alkoxy or (C₁-C₄) alkyl, α- or β-naphthyl or halo (C₁-C₄) alkyl means
reacted in an inert organic solvent. 2. Verfahren gemäß Anspruch 1, dadurch gekennzeichnet, daß in Formel I X und Y jeweils Sauerstoff und R¹ und R² jeweils (C₁-C₄)Alkyl bedeuten.2. The method according to claim 1, characterized in that in formula I X and Y are each oxygen and R¹ and R² are each (C₁-C₄) alkyl. 3. Verfahren gemäß Anspruch 1 oder 2, dadurch gekennzeichnet, daß man als inertes organisches Lösungsmittel einen Alkohol, ein Keton, einen Ether, einen Ester, einen Kohlenwasserstoff, einen halogenierten Kohlenwasserstoff, ein Nitril oder eine Mischung aus wenigstens zwei der vorstehenden Lösungsmittel verwendet.3. The method according to claim 1 or 2, characterized in that an alcohol, a ketone, an ether, an ester, a hydrocarbon, a halogenated hydrocarbon, a nitrile or a mixture of at least two of the above solvents is used as the inert organic solvent. 4. Verfahren gemäß einem oder mehreren der Ansprüche 1-3, dadurch gekennzeichnet, daß als Lösungsmittel Diethylether, Aceton, Methylisobutylketon, Essigsäuremethylester, Toluol oder eine Mischung aus wenigstens zwei dieser Lösungsmittel verwendet wird.4. The method according to one or more of claims 1-3, characterized in that diethyl ether, acetone, methyl isobutyl ketone, methyl acetate, toluene or a mixture of at least two of these solvents is used as solvent. 5. Verfahren gemäß einem oder mehreren der Ansprüche 1-4, dadurch gekennzeichnet, daß man als Salze der Verbindung der Formel II solche der Fluor-, Chlor-, oder Bromwasserstoffsäure oder der Schwefel- oder Phosphorsäure verwendet.5. The method according to one or more of claims 1-4, characterized in that the salts of the compound of formula II used are those of hydrofluoric, chloric or hydrobromic acid or sulfuric or phosphoric acid. 6. Verfahren gemäß einem oder mehreren der Ansprüche 1-5, dadurch gekennseichnet, daß man bei Reaktionstemperaturen von 0-180 °C arbeitet.6. The method according to one or more of claims 1-5, characterized gekennseichnet that one works at reaction temperatures of 0-180 ° C. 7. Verfahren gemäß einem oder mehreren der Ansprüche 1-6, dadurch gekennzeichnet, daß man bei Reaktionstemperaturen von 20-140 °C arbeitet.7. The method according to one or more of claims 1-6, characterized in that one works at reaction temperatures of 20-140 ° C. 8. Verfahren gemäß einem oder mehreren der Ansprüche 1-7, dadurch gekennzeichnet, daß man die Reaktion unter Inertgasatmosphäre durchführt.8. The method according to one or more of claims 1-7, characterized in that one carries out the reaction under an inert gas atmosphere.
EP87118369A 1986-12-16 1987-12-11 Process for the preparation of aminopyrimidines Expired - Lifetime EP0271833B1 (en)

Applications Claiming Priority (2)

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DE19863642832 DE3642832A1 (en) 1986-12-16 1986-12-16 METHOD FOR PRODUCING AMINOPYRIMIDINES
DE3642832 1986-12-16

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EP0445642A1 (en) * 1990-03-08 1991-09-11 BASF Aktiengesellschaft 2-Amino-(fluoralkoxy-pyrimidines) and process for their preparation
EP0547411A1 (en) * 1991-11-26 1993-06-23 Lonza A.G. Process for the preparation of 2-substituted 4,6-dialkoxypyrimidines

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DE4007683A1 (en) * 1990-03-10 1991-09-12 Basf Ag HERBICIDAL SULFONYL UREAS, METHODS AND INTERMEDIATE PRODUCTS FOR THEIR PRODUCTION
DE4024761A1 (en) * 1990-08-03 1992-02-06 Basf Ag 2-AMINO- (FLUORALKOXY-1,3,5-TRIAZINE) AND METHOD FOR THE PRODUCTION THEREOF
DE4024754A1 (en) * 1990-08-03 1992-02-06 Basf Ag HERBIC SULFONYL HARBONS, METHOD AND INTERMEDIATE PRODUCTS FOR THEIR PREPARATION AND THEIR USE
US5208337A (en) * 1990-09-15 1993-05-04 Hoechst Aktiengesellschaft Process for the preparation of aminopyrimidines
EP0689238B1 (en) * 1994-06-23 2002-02-20 STMicroelectronics S.r.l. MOS-technology power device manufacturing process
EP1200414B1 (en) * 1999-04-15 2005-04-20 Basf Aktiengesellschaft Process for the preparation of substituted pyrimidines
US6281358B1 (en) 1999-04-15 2001-08-28 American Cyanamid Company Process for the preparation of substituted pyrimidines
CN110818643B (en) * 2018-08-13 2021-04-16 新发药业有限公司 Preparation method of 2-amino-4, 6-dimethoxypyrimidine

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Publication number Priority date Publication date Assignee Title
EP0445642A1 (en) * 1990-03-08 1991-09-11 BASF Aktiengesellschaft 2-Amino-(fluoralkoxy-pyrimidines) and process for their preparation
US5283332A (en) * 1990-03-08 1994-02-01 Gerhard Hamprecht 2-amino(fluoroalkoxy)pyrimidines and the preparation thereof
US6235904B1 (en) * 1990-03-08 2001-05-22 Basf Aktiengesellschaft 2-amino (fluoroalkoxy) pyrimidines and the preparation thereof
EP0547411A1 (en) * 1991-11-26 1993-06-23 Lonza A.G. Process for the preparation of 2-substituted 4,6-dialkoxypyrimidines

Also Published As

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EP0271833A3 (en) 1990-02-28
DE3642832A1 (en) 1988-06-30
US4831138A (en) 1989-05-16
JPS63162677A (en) 1988-07-06
DE3750500D1 (en) 1994-10-13

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